RNF121

Chr 11

ring finger protein 121

NCBI Gene: 55298 ENSG00000137522 UniProt: Q9H920

RNF121 encodes an E3 ubiquitin ligase that promotes degradation of misfolded endoplasmic reticulum proteins through the ERAD pathway and may regulate the unfolded protein response to reduce ER stress. The gene shows high constraint against loss-of-function variants (LOEUF 0.487), suggesting intolerance to haploinsufficiency. However, no definitive human disease associations have been established for RNF121 mutations at this time.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Several alternatively spliced transcript variants have been noted for this gene, however, not all are likely to encode viable protein products. [provided by RefSeq, Sep 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.319

Z-score 3.31

OE 0.23 (0.12–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.39Z-score

OE missense 0.72 (0.62–0.83)

137 obs / 191.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.12–0.49)

0≤0.351.4

Missense OE?0.72 (0.62–0.83)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 5 / 21.6Missense obs/exp: 137 / 191.1Syn Z: 0.65

Background carrier burden — how many people carry a rare variant somewhere in RNF121?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

374 rare PASS variants

Rare truncating (LoF)

1 in 4,200

45 rare PASS variants

Rare synonymous (reference)

1 in 440

138 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RNF121. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 380	1 in 8,100
South Asian	~43k	1 in 230	1 in 1,600
Remaining (unassigned)	~30k	1 in 310	1 in 4,800
European (Finnish)	~27k	1 in 780	≈ 1 in 8,300
Admixed American	~22k	1 in 260	≈ 1 in 5,900
African / African American	~21k	1 in 210	≈ 1 in 5,300
East Asian	~20k	1 in 170	≈ 1 in 4,900
Ashkenazi Jewish	~13k	≈ 1 in 3,200	none seen
Middle Eastern	~2,884	1 in 320	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 9.? see exons ↓